Polyol pathway, 2,3-diphosphoglycerate in erythrocytes and diabetic neuropathy in rats

Despite substantial data on radioligand binding to the sigma receptor, neither the physiologic function nor the intracellular mechanism of this receptor is known. In this study, we examined the effect of sigma ligands on Ca++ influx induced by N-methyl-D-aspartate (NMDA) in single primary cultured rat frontal cortical neurons with fluorescence video microscopy. All sigma ligands tested reduced the NMDA-induced increase in intracellular Ca++ concentration ([Ca++]i) in a dose-dependent manner with IC50 values in the low micromolar range. Inhibition by haloperidol and (+)-N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1-ethyl-but-3-en-1-ylam ine hydrochloride (JO1784) was noncompetitive; but, exogenous glycine (100 microM) did not alter their IC50 values. In addition, haloperidol (1 microM) enhanced Mg+(+)-mediated inhibition of the NMDA-induced [Ca++]i increase (IC50 = 0.45 +/- 0.01 mM vs. an IC50 = 0.98 +/- 0.06 mM for Mg++ alone). Selective sigma receptor ligands (JO1784, (+)-pentazocine) caused a greater reduction of the sustained phase of the Ca++ response to NMDA, whereas haloperidol and DTG reduced both the initial and sustained phase of the response to a similar degree. The rank order of potencies for inhibition of both the sustained Ca++ response phase and (+)-[3H]SKF-10047 binding (Roman et al., J. Pharm. Pharmacol. 42: 439-440, 1989) were similar. These findings suggest that sigma 1 ligands indirectly modulate NMDA receptor complex function through sigma 1 receptors and that sigma ligands facilitate the desensitization of the Ca++ response to NMDA.     

On case-based learnability of languages

Case-based reasoning is deemed an important technology to alleviate the bottleneck of knowledge acquisition in Artificial Intelligence (AI). In case-based reasoning, knowledge is represented in the form of particular cases with an appropriate similarity measure rather than any form of rules. The case-based reasoning paradigm adopts the view that an Al system is dynamically changing during its life-cycle which immediately leads to learning considerations. Within the present paper, we investigate the problem of case-based learning of indexable classes of formal languages. Prior to learning considerations, we study the problem of case-based representability and show that every indexable class is case-based representable with respect to a fixed similarity measure. Next, we investigate several models of case-based learning and systematically analyze their strengths as well as their limitations. Finally, the general approach to case-based learnability of indexable classes of formal languages is prototypically applied to so-called containmet decision lists, since they seem particularly tailored to case-based knowledge processing.     

Regression of superficial gastric MALT lymphoma with unsuccessful eradication therapy for Helicobacter pylori infection

A 51-year-old man had a reddish flat granular lesion in the stomach on endoscopic examination. Histology of biopsied specimen confirmed the diagnosis of low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (gastric MALT lymphoma) and simultaneous infection with Helicobacter pylori. He was given antibiotic treatment. Five weeks later, endoscopy and histology of biopsied specimen showed eradication of H. pylori, and the tumor had regressed. Six months later, H. pylori reemerged, but the tumor had not recurred. After the second antibiotic therapy, H. pylori has been eradicated. The lymphoma has been in remission for 14 months.     

Molecular cloning, expression, and functional characterization of novel mouse sulfotransferases

STUDY OBJECTIVE: The present study was performed to determine the influence of a perioperative myocardial infarction on long-term mortality in patients who have undergone elective vascular surgery. STUDY DESIGN: This was a 4-year follow-up of patients who had undergone elective vascular procedures at a Veterans Affairs Medical Center. Between January 1989 and December 1990, 115 consecutive patients underwent surgery for either an expanding abdominal aortic aneurysm (AAA) (38%) or for pain in the lower extremities (62%). RESULTS: Vital status at 4 years postsurgery was determined for all patients. Thirty-day postoperative mortality was 3%, while estimates at 1, 2, 3, and 4 years were 19%, 26%, 35%, and 39%, respectively. Of the 45 patients who died within 4 years following surgery, the major causes of death were cardiac (40%), cancer (18%), cerebrovascular (13%), and peripheral vascular disease (11%). Univariate predictors of 1-year mortality on preoperative evaluation were an abnormal ECG, moderate or greater sized exercise thallium defect and left ventricular ejection fraction < or =40%, and a perioperative myocardial infarction. Univariate predictors of 4-year mortality were non-AAA surgery and diabetes mellitus. Perioperative myocardial infarction was a marginally significant independent predictor of 1-year mortality (p=0.06), while the need for non-AAA surgery was a strong independent predictor at 4 years. CONCLUSIONS: Cardiac mortality is the major cause of late death among patients undergoing elective vascular surgery. Although preoperative indicators of symptomatic coronary artery disease and nonfatal perioperative myocardial infarction identified those individuals at increased mortality in the first postoperative year, the extent of vascular disease at presentation may be a more important determinant of long-term survival. A randomized trial in such patients is needed to assess the best strategy for treating patients with coexistent coronary artery and vascular diseases.     

A quantitative analysis of time-decay reproducible stress-inducedleakage current in SiO2 films

In the cases of both Fowler-Nordheim (FN) stress and substrate hot-hole stress, three reproducible stress-induced leakage current (SILC) components have been found for the repeated unipolar gate-voltage scans in 9.2 nm wet oxides. To clarify the mechanisms of these current components, a quantitative analysis has been developed. By precisely modeling the phonon assisted tunneling process, it has been shown that the E-J and t-J characteristics of the reproducible current components can be completely simulated as electron tunneling processes into the neutral traps, each with a single trap level. From this analysis, the physical parameters of the traps have been estimated with a reasonable degree of accuracy. Furthermore, the increase in distribution of the neutral trap density toward both the SiO₂ interfaces has also been estimated     

Mechanism of an early lysis by fatty acids from axenic Phormidium tenue (musty odor-producing cyanobacterium) and its growth prolongation by bacteria

We have previously demonstrated that bacteria-containing Phormidium tenue, a cyanobacterium which produces musty odor 2-methylisoborneol, grew beyond 8 weeks, whereas axenic alga perished suddenly between the 3rd week and the 4th week while being cultured in the laboratory. This mechanism was investigated. It is assumed that when algal cells grow beyond a certain level, the supply of CO2 becomes inadequate and results in the rapid lysis of axenic alga. At that time, inhibitory substances liberated from algal cells kill the surviving alga. Since the process occurs continuously, this alga is finally annihilated. On the other hand, since inhibitory substances are metabolized or degraded by bacteria coexistent with alga, bacteria-containing P. tenue maintains growth for a long time. The growth-inhibitory substance was found to be unsaturated free fatty acids.     

Troglitazone prevents the inhibitory effects of inflammatory cytokines on insulin-induced adipocyte differentiation in 3T3-L1 cells

Tumor necrosis factor (TNF) is implicated in wasting syndromes and insulin resistance in chronic infection and obese-linked diabetes. TNF (10 ng/ml) inhibited adipocyte differentiation of 3T3-L1 cells, and in these TNF treated cells little insulin-stimulated glucose uptake was observed. Treatment of 3T3-L1 cells with troglitazone (1-10 microM) partially prevented this inhibitory effect of TNF on adipogenesis, and enhanced expression of C/EBP alpha and GLUT4, even in the presence of TNF. Troglitazone also prevented the inhibitory effects of interleukin-1, interleukin-6, and leukemia inhibitory factor, but not of transforming growth factor beta on adipocyte differentiation of 3T3-L1 cells. These effects might contribute to the antidiabetic effect of troglitazone in obese diabetic animals.